We have shown that lymphocytic choriomeningitis virus (LCMV) infection, poly I:C, and interferon beta and gamma induce in vivo the blastogenesis, turnover rate, and proliferation of mouse natural killer (NK) cells. In the next year, we will focus our studies on the nature of the NK cells and NK cell precursors that proliferate and on factors involved with influencing the proliferation. NK cells will be quantitated using a fluorescence-activated cell sorter (FACS) by the double labeling technique with antibodies to asialo GM1 and NK alloantigen. Rat monoclonal antibodies to NK cells will be generated by priming rats with partially purified NK cells. The proliferation of NK cells in interferon-stimulated mice will be compared between old versus young and genetically-high NK versus low NK strains. By limiting dilution clonal analysis, the number of cells giving rise to NK cells will be monitored under conditions of interferon stimulation in vivo and culturing with IL-2 supernatants in vitro. The size and antigenic nature of the clone precursors will be determined. This will allow one to determine if cells with NK clone-producing potential expand in number during virus infections. High dose LCMV infection results in very high levels of interferon in vivo but low levels of NK cell blastogenesis. Experiments will determine if high doses of interferon inhibit NK cell blastogenesis, whereas low doses enhance it. (SR)